Irremediable Complexity: Notes from Ford Doolittle's seminar talk

While I work on polishing up Part II of the Neutral Evolution series, thought I'd write up and post my four pages of notes from Ford Doolittle's seminar talk today yesterday, while I can still remember what my scribbles were supposed to mean. As there's no unpublished data there, and a long-awaited paper on the subject has just been submitted, I believe it should be fair game for blogging. Coming from a vicious field (Arabidopsis, sigh...), I'm generally rather cautious about blogging department talks and such, but Constructive Neutral Evolution is a subject in need to spreading, and not a particularly competitive area at the moment...

Rosie has another summary of today's yesterday's talk, with an executive summary therein; she tried to scoop me, so clearly this means I must outdo her in length and verbosity =P

[If anything doesn't make sense, it's very likely an error on my part]
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Irremediable Complexity - Ford Doolittle, 07 Apr 2010
[paraphrased from notes; own comments in grey]
- Is each step in the evolution of a complex machine useful?

Irremediable complexity involves three factors: Tinkering, small populations, ratchets (Constructive Neutral Evolution). [prior to that, must discuss common views on complexity first]

Common views on complexity
- Directionality: 19th century - divine forces guide evolution; 20th century - orthogenesis - evolution exhibits a drive towards perfection (and complexity)
- Progress: Life started off being simple and became increasingly complex
But is there necessarily a trend?
(Gould 1996 Full House) The Drunkard's Walk: if one starts off at a limit that cannot be passed, random steps will eventually lead away from this limit. Presumably, life began more or less at the lower limit of complexity (specialised parasites aside), so it's bound to get more complex as it's the only way to go.
In fact, complexity is increased only in a few lineages, which also happen to be the ones we really like to look at.

So is the evolution of multicellular animals and plants from choanoflagellate-like and chlamydomonas-like organisms, respectively, a drunkard's walk or driven by something (eg. selection)?

Selectionist explanations
- Accumulation of specific adaptations results in complexity (eg. The Eye)
Another example: larger genome size is an adaptation for more gene regulation which is required in more complex organisms. [Note: C-value paradox, etc] Molecular biologists have an obsession with 'mystery DNA' having regulatory roles...
- Arms races, sexual selection
Greater biodiversity/more competition between organisms stimulates greater complexity, eg through niche specialisation and sex selection
- Evolving evolvability
Outdoing one's environmental changes by evolving faster. Eg. Exon shuffling as a function of introns: introns space out exons allowing more novel combinations of these exons to occur, which may be adaptive.
Caveat with evolvability -- it's a clade-selection level trait, not individual level.

Neutral forces - should be our null hypotheses
- Tinkering (François Jacob) -- will still have traces of an apparatus' past functions along with new ones --> life is full of Rube Goldberg machines.
- Small population size -- mildly deleterious traits more likely to be fixed in smaller populations (Michael Lynch; more info in Part I of my Neutral Evolution series) Eukaryotes are a case of smaller population size relative to prokaryotes.
- Ratchets -- 1. Maynard-Smith & Szathmary's Major Transitions; 2. Stoltzfus & Covello's Constructive Neutral Evolution

Major Transitions: There are steps in evolution that are difficult or impossible to reverse -- act as ratchets.

Constructive Neutral Evolution: a previously fortuitous (non-functional) interaction can enable an otherwise-deleterious mutation to occur, resulting in a dependency upon this interaction. [a diagram is in the making]

More interactions evoke more opportunity for Constructive Neutral Evolution to drive (via ratchetting) an increase in complexity. [thus, the result would be an explosion of complexity past a certain threshold]
The dependency can be built up by other mutations, thus further solidifying the requirement for a given interaction.
Note that no positive selection is required at any step [only purifying], would also be more drastic in smaller populations where more deleterious mutations are fixed by drift. That said, positive selection can still play a role in parallel.

Examples:
Lambowitz's maturase-requiring group I self-splicing intron. [will be discussed in further detail in impending post] A derived Neurospora lineage requires a maturase for the splicing of group I introns whereas nearby relatives do not. Lambowitz later (2006) argues that maturase-mediated splicing evolved in response to the splicing problem, as opposed to enabling it to arise. This is putting the cart before the horse.

kDNA editosome (Trypanosomes et al.)
[Can be summed up in one interjection: whyyyyyyyyyyyyy???]
In summary, genes coded by the mitochondrial genome are non-sensical, and right after transcription the pre-mRNAs are edited by the complicated process involving templates and inserting various U's where they are needed.

There are several explanations that have been proposed:
- relic of the RNA world -- for starters, tryps are derived.
- to correct pre-existing mutations -- backwards logic again (cart before the horse)
- regulation
[Digression to discuss the two oft-conflated meanings of function]
1. Selected function -- how a trait got to be there
2. Current function -- what happens if trait is removed

Example from Maynard-Smith: Stiff back of the horse. Removal thereof would prevent humans from riding it, but no one can argue that the horse's back evolved so that humans could ride it in the future!

How editing really arose -- CNE [see Stoltzfus 1999 JME and Lukes et al 2009 PNAS(and subsequent correspondence)]: once the process started, it couldn't be reversed, thus complexity reached an absurd level.
"Absurdly complex spliceosome"
- if you think about it, it's "incredibly stupid" to have such a complex machine for removing introns
- cites "Five Easy Pieces" Sharp 1991 Science laying out a hypothesis for the evolution of group II introns
- see Lambowitz example for how the spliceosome may have arisen through initially-neutral protein interactions

Ribosome
Also by CNE. Roughly put, the RNA does most of the enzymatic work in the ribosome, with the proteins taking on more of a structural function. Presumably, initially the ribosome could've been entirely a ribozyme, picking up various proteins for supporting structural roles, like the Lambowitz intron, with the help of constructive neutral evolution.

Cited TW O'Brien 2003 IUBMB Life paper: the mammalian mitochondrial ribosome is smaller than that of its host (eukaryotic) yet larger than the prokaryotic counterpart; furthermore, many of the extra mitochondrial ribosomal proteins do not come from the eukaryote! This is a great example of convergence between the two separate evolutionary paths, both starting off with the small (at least in terms of protein count) prokaryotic ribosome and becoming bloated in complexity. Furthermore, mitochondria also have a greatly reduced effective population size, thereby encouraging the accumulation of complexity, unlike in their free-living bacterial brethren. [would be interesting to compare plastid, mitochondrial and eukaryotic ribosomal evolution, controlling for LGT, replacement, loss, and all the other crap associated with endosymbiosis, of course. A nice system with at least two independent replicates originating from very distantly-related sources]

[Another guy (unsure about citing personal communications without their knowledge) rather eloquently put it along the lines of "The rRNA was fully functional enzymatically on its own until the other shit stuck along for the ride"]


In closing, tinkering leads to klunkiness, smaller populations allow more mildly deleterious mutations, and ratchets make complexity ultimately unavoidable.

For another example of irremediable complexity, think what would happen if an institution was formed with a few small committees with specific functions and left alone for a few decades. Like a university. The bureaucracy and administrative complexity would increase while the overall efficiency of the system wouldn't benefit much. One can think of the complex biochemical pathways as "cellular bureaucracy".

"Complexity is unavoidable and largely irremediable: Resistance is useless"


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My initial impression of Ford Doolittle came from the whole 'missing Tree of Life' debacle, where he did appear rather rash and extremist, perhaps largely due to the media portrayal and associated uproar -- after his seminar talk and a more informal chat at lunch, I fully retract my first impressions, and must say that he's actually quite reasonable and not radical or extremist at all (and very pleasant and interesting to talk to). Naturally, science reporters reporters in general tend to hyperpolarise any slightest argument they chance upon, and turn anyone with a shred of an opinion into a flaming radical; thus it was another lesson to be extremely cautious about impressions you get about someone based on someone else's reporting. But another thing I've noticed is he seems less assertive in person than in his own papers as well. Well-balanced and subtle ideas seldom get the attention they deserve, so they must often be blown out of proportion to be at all noticed.

Perhaps this is another reason neutral theories remain so obscure: the adaptationists are occupied with explaining natural selection to creationists et al., thereby being much noisier and noticeable. The more balanced pluralists don't have much extremist thought to push, so they tend to get ignored (I find the Stoltzfus 1999 paper to be quite subtle and unassertive; perhaps that's why it was largely ignored).

Back to the ToL kerfuffle: If one were to say "LGT is very frequent in bacterial populations and may pose very substantial problems to reconstructing bacterial phylogeny and the deep history of life, perhaps even posing a valid question of whether such a phylogeny may truly ever be found", the statement is too reserved and subtle to make much of a splash beyond a small circle of specialists. However, if one goes all out and shouts "The Tree of Life is dead!", people actually turn around and look. Many misinterpret the message and get their own strange notions on the subject (often believed much more strongly than by the originator of the idea...), but at least some people get it and consider the problem.

Furthermore, the "Darwin was wrong" slant was intended to signal that we should get away from our Darwin fetish. I fully agree. Darwin was a great scientist, but it is outright immoral to ignore the hard work of thousands of people who came after him, and the thousands who are working in the field right now. Darwin may have sparked the field, but he is certainly not its most important element. The term "Darwinism" is vacuous and misleading, and should be abandoned soon. Furthermore, who cares what creationists think? Some of us are sick of having to change our vocabulary just because some religious idiot with an agenda could abuse it. The primary role of evolutionary biologists is to study evolutionary biology; educating the public is secondary (while still important); dealing with creationists is about last. Science educators are responsible for that. We cannot fight religion, especially its fundamentalist forms, with reason (hence why Dawkins fails at it). So what if they misunderstand and misrepresent Darwin? People misunderstand and misrepresent quantum mechanics even more, and yet physicists don't seem to lose sleep over it.

Political agendas will always be there; textbooks will always be influenced by the political (and sadly, religious) climate of the times. It sucks, but such is reality. History and the social sciences are also badly mangled in schools (eg. communism is still a topic not only taught entirely wrong, but also characterised by a blunt refusal to listen to those who may know better). After all, to understand science effectively, one must appreciate the subject, and be willing to not only accept, but commit work to it. The unwilling will never learn unless they want to. What is of a much higher importance than defending Darwin is promoting the overall public image of science and academia in general, and making academic activity 'cool' in the eyes of the public. If scientists were well-respected in 1970's Russia, there's no reason we can't acheive that again and in a different society. But it will take work.

But to get that to work, we must strive to suppress our polarising tendencies and recognise that often people's opinions are more subtle than they appear. We must also pay greater attention to ideas that are not pushed as aggressively as others, such as constructive neutral evolution. Those may well be more refined and ready for acceptance than the ideas cast in apparent simplicity and loudness.

References:
O'Brien, T. (2003). Properties of Human Mitochondrial Ribosomes IUBMB Life (International Union of Biochemistry and Molecular Biology: Life), 55 (9), 505-513 DOI: 10.1080/15216540310001626610

Sharp PA (1991). "Five easy pieces". Science (New York, N.Y.), 254 (5032) PMID: 1948046

Stoltzfus, A. (1999). On the Possibility of Constructive Neutral Evolution Journal of Molecular Evolution, 49 (2), 169-181 DOI: 10.1007/PL00006540